Medical Disclaimer
  • Educational Only: Not for clinical decision-making.
  • Verify Information: Always consult protocols and authoritative sources.
AI Assistance Notice
AI was used to assist in organizing and formatting this information. All content is reviewed for accuracy.
Bedside Snapshot
  • Water-soluble, rapid-onset benzodiazepine used for procedural sedation, RSI adjunct, short-term anxiolysis, treatment of seizures/status epilepticus, and continuous infusions for ICU sedation.
  • IV onset: 1–3 minutes; peak ~3–5 minutes; duration after a small bolus typically 30–60 minutes, but context-sensitive half-life can be much longer with infusions or in organ dysfunction.
  • Procedural sedation (adult): 0.5–2 mg IV initially, then 0.5–1 mg IV q2–3 minutes until desired effect (commonly total 2–5 mg in healthy adults), given with full cardiorespiratory monitoring and airway readiness.
  • RSI co-induction / post-intubation sedation: 0.02–0.1 mg/kg IV (often 1–5 mg increments) for amnesia and sedation, usually combined with analgesia and sometimes other sedatives.
  • Status epilepticus: 0.2 mg/kg IM midazolam is a common prehospital regimen; in-hospital, 0.1–0.2 mg/kg IV (max 10 mg) may be used if IV access is available, following local SE protocols.
  • ICU sedation: Loading 0.02–0.1 mg/kg IV then infusion 0.02–0.1 mg/kg/h; however, continuous midazolam is associated with prolonged ventilation and delirium, so many guidelines favor propofol or dexmedetomidine when feasible.
  • Major concerns: Respiratory depression, hypotension (especially in shock or with other sedatives), delirium with prolonged use, and accumulation in renal failure due to active metabolites.
Brand & Generic Names
  • Generic Name: Midazolam
  • Brand Names: Versed, multiple generics
Medication Class

Short-acting benzodiazepine; sedative-hypnotic, anxiolytic, amnestic, anticonvulsant

Pharmacology

Mechanism of Action:

  • Binds to benzodiazepine sites on the GABAA receptor complex, enhancing the affinity of the receptor for GABA and increasing the frequency of chloride channel opening
  • Leads to neuronal hyperpolarization and decreased excitability, producing anxiolytic, sedative, hypnotic, amnestic, and anticonvulsant effects
  • Does not directly activate GABAA receptors; requires endogenous GABA, contributing to a wide safety margin compared with barbiturates

Pharmacokinetics (IV):

  • Onset IV: 1–3 minutes, with peak effect at ~3–5 minutes
  • Duration: After a small bolus typically 30–60 minutes, but context-sensitive half-life increases significantly with prolonged infusions
  • Distribution: Highly lipophilic at physiologic pH; large volume of distribution; rapid CNS penetration
  • Metabolism: Hepatic CYP3A4-mediated oxidation to 1-hydroxymidazolam (active), which is then glucuronidated. The glucuronide metabolite is pharmacologically active and accumulates in renal impairment
  • Elimination Half-Life: ~1.5–3 hours after a single bolus in healthy adults, but much longer with continuous infusions, obesity, hepatic dysfunction, or renal failure
Indications
  • Procedural sedation for painful or anxiety-provoking procedures (e.g., fracture reduction, cardioversion, endoscopy) in combination with analgesics
  • Pre-induction anxiolysis and amnesia prior to RSI or OR induction
  • Adjunctive sedative in mechanically ventilated patients when other agents are insufficient or contraindicated
  • Acute seizure management and status epilepticus (IV, IM, IN, or buccal routes depending on access and setting)
  • Sedation for noninvasive ventilation or other respiratory support when careful titration and monitoring are possible
Dosing & Administration

Available Forms:

  • IV/IM solution: Typically 1 mg/mL, 5 mg/mL in vials or prefilled syringes
  • Intranasal and buccal use: Off-label using IV solution administered via atomizer or buccal syringe
  • Oral solution or syrup: For pediatric procedural anxiolysis in some settings (less common in ICU practice)

Dosing – Midazolam (Adult, Always Follow Local Protocol):

Indication Dose & Route Frequency / Titration Notes
Procedural sedation (healthy adult, IV) 0.5–2 mg IV initially Then 0.5–1 mg IV q2–3 min to effect (commonly total 2–5 mg) Reduce doses in elderly, frail, or hemodynamically unstable patients
Pre-induction / pre-procedure anxiolysis 1–2 mg IV (or 0.02–0.04 mg/kg) Single dose, may repeat small doses Titrate slowly; monitor for respiratory depression
Status epilepticus – IV (in-hospital) 0.1–0.2 mg/kg IV (max 10 mg) May repeat per protocol Alternative: 0.2 mg/kg IM or IN in prehospital settings
ICU sedation – loading dose 0.02–0.1 mg/kg IV Give over several minutes Use lower end in shock, elderly, or with other sedatives
ICU sedation – continuous infusion 0.02–0.1 mg/kg/h IV Titrate to sedation target (e.g., RASS –2 to 0) Prolonged infusions ↑ risk of delirium and accumulation
No Strict Maximum: No strict maximum dose exists, but toxicity increases with prolonged high doses. Frequent reassessment is needed. Consider alternative sedatives for long-term ICU sedation.
Contraindications

Contraindications:

  • Acute narrow-angle glaucoma (class warning for benzodiazepines)
  • Severe respiratory depression or unstable airway without ventilatory support
  • Hypersensitivity to midazolam or other benzodiazepines

Major Precautions:

  • Risk of respiratory depression and apnea, especially with opioids, propofol, or in patients with underlying lung disease
  • Hypotension, particularly in hypovolemic, septic, or cardiogenic shock patients; support BP with fluids and vasopressors as needed
  • Delirium and prolonged sedation with continuous infusions; minimize duration and daily perform sedation interruptions when appropriate
  • Accumulation of active glucuronidated metabolite in renal failure can prolong sedation even after stopping the infusion
  • Potential for tolerance, dependence, and withdrawal with prolonged high-dose use; taper if used for more than a few days
Respiratory Depression Risk: Midazolam can cause apnea and respiratory arrest, especially with rapid IV push or when combined with other sedatives (opioids, propofol). Always have airway equipment ready and monitor continuously with pulse oximetry and capnography.
Adverse Effects

Common:

  • Sedation, drowsiness, dizziness
  • Hypotension (mild to moderate)
  • Respiratory depression (dose-dependent)
  • Injection site pain or phlebitis

Serious:

  • Apnea and respiratory arrest, especially with rapid IV push or combined sedatives
  • Severe hypotension and cardiovascular collapse in unstable patients
  • Paradoxical agitation or disinhibition (more common in pediatrics or elderly)
  • Withdrawal seizures or severe agitation if abruptly stopped after prolonged high-dose infusions
  • ICU delirium with prolonged infusions
Special Populations

Elderly Patients:

  • Increased sensitivity to benzodiazepines
  • Use lower initial doses (0.5–1 mg IV for sedation)
  • Titrate slowly and monitor closely for respiratory depression
  • Higher risk of delirium, falls, and prolonged sedation

Hemodynamically Unstable / Shock:

  • Use lower doses (0.5–1 mg IV increments)
  • Support blood pressure with fluids and vasopressors as needed
  • Consider ketamine as alternative for procedural sedation in shock

Hepatic Impairment:

  • Reduced clearance and prolonged half-life
  • Use lower doses and extend dosing intervals
  • Monitor for prolonged sedation

Renal Impairment:

  • Active glucuronide metabolite accumulates in renal failure
  • Prolonged sedation even after stopping continuous infusions
  • Use lower doses and allow longer recovery time
  • Avoid continuous infusions when possible in severe renal impairment

Obesity:

  • Use ideal or adjusted body weight for dosing, not total body weight
  • Prolonged duration due to increased volume of distribution

Pregnancy & Lactation:

  • Pregnancy Category D: Risk of fetal harm; use only if benefits outweigh risks
  • May cause neonatal sedation, respiratory depression, and withdrawal
  • Lactation: Excreted in breast milk; use with caution
Monitoring

During Procedural Sedation:

  • Continuous pulse oximetry and, when available, capnography for any parenteral use aimed at moderate/deep sedation
  • Frequent blood pressure and heart rate monitoring
  • Airway patency and respiratory adequacy

ICU Sedation:

  • Continuous monitoring in unstable patients or on infusions
  • Sedation depth with validated scales (e.g., RASS)
  • Daily delirium screening (CAM-ICU or similar)
  • Renal and hepatic function for patients on continuous infusions

Withdrawal Monitoring:

  • Signs of benzodiazepine withdrawal when tapering after prolonged use
  • Agitation, tremor, seizures, autonomic instability
Clinical Pearls
Go Slow in Vulnerable Patients: Give midazolam slowly in small increments (especially in elderly or hypotensive patients) to avoid sudden apnea or hypotension. Start with 0.5–1 mg IV and wait 2–3 minutes before giving more. It's much easier to give more than to reverse too much.
Pair with Analgesia for Procedures: For brief procedures, consider pairing small midazolam doses with short-acting opioids (fentanyl) or ketamine rather than escalating the benzodiazepine alone. Midazolam provides sedation and amnesia but no analgesia.
Avoid Prolonged ICU Infusions: Continuous midazolam infusions are best reserved for situations where other sedatives are contraindicated or inadequate. Otherwise, propofol or dexmedetomidine may shorten ICU stay and reduce delirium risk. PADIS guidelines recommend minimizing benzodiazepine use in ICU.
Flumazenil Reversal: Flumazenil can reverse benzodiazepine effects but should be used cautiously, especially in chronic benzo users (risk of severe withdrawal and seizures) or those with seizure risk. Provide supportive care and airway management instead when possible.
Active Metabolites in Renal Failure: The active glucuronide metabolite accumulates in renal failure, leading to prolonged sedation even after stopping continuous infusions. In ESRD or severe AKI, patients may stay sedated for days after midazolam is stopped. Plan accordingly.
Taper After Prolonged Use: If midazolam has been used for more than a few days at moderate-high doses, don't stop abruptly. Taper gradually over several days to avoid withdrawal seizures, severe agitation, or autonomic instability.
IM/IN for Status Epilepticus: For prehospital or difficult IV access status epilepticus, 0.2 mg/kg IM or IN midazolam is highly effective and faster than establishing IV access for diazepam or lorazepam. Many EMS protocols now favor IM/IN midazolam as first-line.
Paradoxical Reactions: Some patients (especially children, elderly, or those with developmental disabilities) may experience paradoxical agitation, aggression, or disinhibition with benzodiazepines. If this occurs, stop the drug and use alternative sedation.
Context-Sensitive Half-Life: After a single small bolus, midazolam wears off in 30–60 minutes. But with continuous infusions or repeated dosing, the context-sensitive half-life increases dramatically due to drug accumulation in peripheral compartments. Recovery can take hours to days.
References
  • 1. Lexicomp. (2025). Midazolam: Drug information. Wolters Kluwer. https://online.lexi.com/
  • 2. Green, S. M., & Krauss, B. (2014). Procedural sedation in emergency medicine. Annals of Emergency Medicine, 63(3), 247–265. https://doi.org/10.1016/j.annemergmed.2013.07.006
  • 3. Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., Arya, R., Bainbridge, J., Bare, M., Bleck, T., Dodson, W. E., Garrity, L., Jagoda, A., Lowenstein, D., Pellock, J., Riviello, J., Sloan, E., & Treiman, D. M. (2016). Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults. Epilepsy Currents, 16(1), 48–61. https://doi.org/10.5698/1535-7597-16.1.48
  • 4. Barr, J., Fraser, G. L., Puntillo, K., Ely, E. W., Gélinas, C., Dasta, J. F., Davidson, J. E., Devlin, J. W., Kress, J. P., Joffe, A. M., Coursin, D. B., Herr, D. L., Tung, A., Robinson, B. R., Fontaine, D. K., Ramsay, M. A., Riker, R. R., Sessler, C. N., Pun, B., ... Jaeschke, R. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine, 41(1), 263–306. https://doi.org/10.1097/CCM.0b013e3182783b72
  • 5. Farkas, J. (2023). Sedation in the ICU. EMCrit Project – Internet Book of Critical Care (IBCC). https://emcrit.org/ibcc/sedation/
Back to Medication Index